MYOCARDIAL EFFECTS OF EARLY THERAPY WITH PERINDOPRIL DURING EXPERIMENTAL CARDIOMYOPATHY

The effects of chronic angiotensin-converting enzyme (ACE) inhibition on intrinsic myocardial contractility of the failing myocardium poorly documented. In the present study, inotropy, lusitropy, and economy of force generation were studied in vitro in papillary muscles from card iomyopathic Syrian hamster (CSH) under early perindopril therapy, i.e. , therapy begun at a stage when experimental heart failure was not yet observed. One-month-old CSH from the dilated strain Bio 53.58 were ra ndomly treated over a 5-mouth period with either the ACE inhibitor per indopril 1 mg/kg/day (n = 11) or placebo (n = 11), and 7 age-matched c ontrols were given placebo. Compared with control, placebo had a lower maximum shortening velocity (V(max)) (p < 0.01) and normalized total force (p < 0.05), and a lower curvature of the force-velocity relation ship (p < 0.01). It has been shown that the higher the value of the cu rvature, the better the myothermal economy of force generation. Compar ed with placebo, perindopril had a 68% inhibition of plasma ACE activi ty and a greater V(max) (p < 0.05), whereas total force/mm2 was simila r. This resulted in a lesser decrease of the curvature compared to con trol (p < 0. 05). Placebo had a decreased peak lengthening velocity an d rate of force decline. However, compared to control, no intrinsic ab normalities of the relaxation phase were observed in either placebo or perindopril when relaxation parameters were corrected for the lower s ystolic performance. These results indicate that (1) the low inotropic state observed in CSH was associated with a depressed lusitropic stat e and a decreased myothermal economy of cardiac contraction; (2) early therapy with ACE inhibitor helped to preserve myocardial contractilit y and economy of force generation; and (3) no intrinsic modification o f relaxation phase was observable in both placebo-treated and perindop ril-treated CSH.